Pharmaceutical solutions comprising dimethyl sulfoxide

ABSTRACT

Novel pharmaceutical solutions and particularly novel pharmaceutical solutions comprising dimethyl sulfoxide (DMSO).

FIELD OF INVENTION

This invention relates to novel pharmaceutical solutions andparticularly novel pharmaceutical solutions comprising dimethylsulfoxide (DMSO).

BACKGROUND OF THE INVENTION

If one rubs a few drops of DMSO on any part of his/her person, it isusually absorbed very rapidly an a taste resembling garlic isimmediately present. This finding subsequently led to a most importantfinding of pharmacologic ability of pure DMSO of various strengths toreduce inflammation and pain in a wide range of conditions to penetrateinto the skin after topical application of DMSO for the lessening ofpain and swelling of inflammation. Many clinicians have reportedparticularly gratifying results by the use of DMSO in the management ofarthritis.

U.S. Pat. No. 3,549,770 teaches the topical application of undiluteddimethyl sulfoxide, and dimethyl sulfoxide with appropriatepharmaceutical diluents, excipients and adjuvants in the treatment oftissue damage, pain, abnormal muscle contraction and vascularinsufficiency.

The facility with which DMSO penetrates the skin and other membranes hasspawned considerable research into the use of DMSO as a vehicle for theadministration of drugs through topical application. In the course ofthat research a number of different products were added to DMSO withranging degrees of success.

U.S. Pat. No. 3,711,606 teaches the use of DMSO as a carrier inconcentrations of 50% and over by weight with a steroid in lotion,cream, gel and ointment forms to penetrate rapidly to and saturate thestratum corneum, the highly resistant "horny layer" of the skin which isthe major barrier to penetration.

According to this patent "The Steroid continues to penetrate through theskin from `this reservoir` in the stratum corneum to the underlyingtissue and into the circulatory system" (Column 3, Line 50-53).

U.S. Pat. No. 3,711,602 also teaches the compositions (creams,suppositories, ointments and gels) for topical application for enhancingtissue penetration of physiologically active agents (for example,physiologically active steroids, antineoplastic agents, antigens,antihistamine agents, neuropharmacologic agents, anti-inflammatoryagents, anticoagulants, vasodilators, ultra-violet screening agents andagents with DMSO.

However, these compositions are extremely greasy and are soley forsurface penetration, very little penetrating deeply into affected areaswhere the greatest need arises. See also U.S. Pat. Nos. 3,551,554;3,740,420; 3,743,727; 3,790,682; 4,369,190 and 3,499,961 and CanadianLetters Patent Nos. 1,001,075; 1,011,255; 1,043,704; 980,252 and1,005,761.

Furthermore these compositions are not suitable where there is a needfor rapid deep penetration of medicine for direct application to anaffected part of the body (joints etc.). In addition, DMSO also captureswater from the skin, being a hydroxyl ion scavenger thereby dehydratingthe skin.

It is therefore, an object of this invention to provide penetratingsolutions, allowing penetration deeply into affected parts of the body,comprising DMSO, preferably another medicine which may be appliedtopically and which rapidly penetrates deeply into the body carrying themedication in the solutions with it while protecting the skin againstdehydration.

Further and other objects of the invention will be realized by thoseskilled in the art from the following summary of the invention anddetailed description of the embodiments thereof.

SUMMARY OF THE INVENTION

According to one aspect of the invention, a deeply and rapidlypenetrating homogeneous solution for topical application causingmedicine to penetrate deeply and rapidly into affected parts of the bodywithout irritating the skin or leaving a greasy film on the skin whenthe solution is applied topically is provided, the solution comprising:

(a) between about 40% and about 85% DMSO by weight of the solution, morepreferably between about 60% and about 70% DMSO by weight of thesolution of most preferably about 65% DMSO by weight of the solution;

(b) a polyalcohol, preferably having 3-5 carbon atoms, for the retentionof moisture in the skin, in one embodiment, glycerol or glycerine;

(c) a dispersant for assisting to disperse the components in solution toprovide a homogeneous solution when applied to the skin and whenpenetrating the skin, in one embodiment propylene glycol;

(d) a medicine, for example Naproxen and Diclofenac dissolved in thesolution;

(e) water.

Because the medicine must be dissolved in the solution, a solubilizingagent may be added to the solution to dissolve the medicament. Forexample, Naproxen is not soluble in DMSO. Therefore, Ethanol is used tosolubilize the Naproxen for addition to the solution. Xylocaine may alsobe added to the solution where desired.

When the penetrating solutions of the invention are employed in topicalapplications unexpected results from treatment therewith are obtained.This is because of the ability of the solution to penetrate quickly anddeeply into the body through the skin and tissue below the point oftopical application. Furthermore, because of the nature of the solution,the skin is not dried out. Where glycerol is employed, glycerol is ahydroxyl radical scavenger (as is DMSO) and assists in the medicinaleffect of the DMSO in the solution. The dispersant propylene glycol isalso a hydroxyl radical scavenger.

The formulations are prepared by combining the requisite amounts of theingredients together (adding solubilizing agents, for example Ethanolwhere Naproxen is to be included). The medicines that may be used withthe DMSO may be manufactured according to the processes taught in thefollowing patents or other such suitable processes.

    ______________________________________                                        NAPROXEN:   Canadian Letters Patent: 1,122,603 1,004,226                                  1,142,957 1,137,108 879,118 879,719                                           936,171 955,600 960,668 960,689 983,517                                       991,655 1,000,725 1,000,726 1,020,575                                         1,124,735                                                         DICLOFENAC: Canadian Letters Patent: 850,133 811,738                                      829,910 918,175 765,432 827,708 1,126,746                                     1,050,565                                                         NIFEDIPINE: Canadian Letters Patent: 981,582 934,758                                      868,911 921,035 1,080,223                                         ______________________________________                                    

The invention will now be illustrated having regard to the followingembodiments and exemplary test cases.

EMBODIMENTS

DMSO with Diclofenac as a treatment for arthritis.

    ______________________________________                                        300        ml         90% DMSO                                                60         ml         glycerine                                               25         ml         propylene glycol                                        100        ml         water                                                   15         ml         ethyl alcohol                                           75         gm         Diclofenac                                              ______________________________________                                    

Solution as a treatment for Psoriasis

    ______________________________________                                        65         ml         90% DMSO                                                3.375      gm         Diclofenac                                              80         ml         H.sub.2 O                                               5          ml         2% Xylocaine                                            250        ml         ethyl alcohol                                           65         ml         glycerine                                               30         ml         propylene glycol                                        5          ml         tar                                                     ______________________________________                                    

DMSO with Diclofenac & Urea as a treatment for Arthritis with added skinprotection.

    ______________________________________                                        325        ml         DMSO 90%                                                70         ml         H.sub.2 O                                               50         gm         Urea                                                    25         ml         Glycerine                                               75         gm         Diclofenac                                              25         ml         Propylene Glycol                                        ______________________________________                                    

Solution for treatment of Herpes

    ______________________________________                                        335        ml         DMSO 90%                                                25         ml         Glycerol                                                25         ml         Propylene glycol                                        100        ml         H.sub.2 O                                               15         ml         Ethyl Alcohol                                           75         gm         Diclofenac                                              ______________________________________                                    

The following case histories are offered where penetrating solutionsaccording to the invention are employed.

In each of the cases set out below, the anti-inflammatories used wereNaproxen or Diclofenac.

CASE 1 Mrs. E. G.-Age 58 Years-Rheumatoid Arthritis

Severe pain in left tarsal joint, then late in May, right foot thenrapidly involved right leg, both shoulders, elbows, and wrists. Wasfirst treated with phenylbutazone, then Naproxen, but four months laterwas becoming severly disabled with acute symptoms particularlyshoulders, wrists and right foot-33 joints involved. Thereafter,treatment with penetrating solution comprising DMSO with Naproxen,Ethanol, water, propylene glycol and glycerine by the topicalapplication thereof. Indocid was administered by mouth. By the nextmonth some improvement in mobility, but shoulders still only slight (10)abduction. Treatment was continued five times daily. Three months laterremarkable improvement in mobility. Three months later, returned to workpart-time.

This patient has shown steady improvement with essentially full returnto range of motion in all joints. Still employs DMSO by itself forflare-ups, can go without medication.

CASE 2 Mrs. B., W.-Age 52 Years-Post Traumatic Arthritis

Ankle-skiing accident with comminuted fracture-repaired by surgicalintervention with numerous screws and plates-one screw later removed.After 13 years of restricted movement and acute pain, patient wasadvised that if she was not prepared to tolerate the pain--the onlyalternatives were fusion or amputation. Began trial with topicalapplication of a penetrating solution of DMSO anti-inflammatories,propylene, glycol, water and glycerine. Within days mobility began toimprove and this was gradually followed by a reduction in pain. Fourmonths later, almost complete return of function and was pain free. Nowonly employs DMSO at irregular intervals.

CASE 3 Mrs. J. F.-Age 52 years-Traumatic Arthritis

Fractured left ankle on three occasions-each repaired by open reduction.Movements severely restricted and pain severe, employed crutches-hasdone so for three years. Began topical treatment with formulation usedin Case 1. After treatment, flexibility and comfort both improving--canbear some weight. A month later, flexibility improving but still a longway to go. However, lateral and medial movement of tarsal joints hadimproved considerably but dorsiflection still quite limited. Four monthslater can finally touch heel to floor. Some months later, ankle greatlyimproved both mobility improved and pain quite tolerable--has been ableto live normally, walks, dances, etc. has had bouts of gouty arthritisin other foot but this is also under satisfactory control.

CASE 4 Mr. H. B.-Age 63 Years-Arthritis

Arthritis in wrists, hands, ankle, feet and back.

Arthritis recurrent exacerbations for 22 years. Has reached the pointwhere wrists and ankles are almost completely ankylosed-very littlemovement obtainable is not able to continue at work. Barely able towalk--began topical application of penetrating solution comprising DMSOanti-inflammatory, propylene glycol, glycerine, water. Improvement wasseen quite rapdily by reduction of effusion and slow increase ofmobility over the years, in spite of exacerbations of acute arthritis,his mobility has increaded until he can walk much better,lifestylecloser to normal.

CASE 5 Mr. M. L.-Age 51 Years-Osteoarthritis

Right knee, began following a football injury 30 years ago-had meniscusexcised. Activities quite limited due to pain. Began topical applicationof penetrating solution comprising DMSO, anti-inflammatory, propyleneglycol, glycerine and water. Exercise tolerance and comfort improvedsteadily. Patient has been able to participate in sports in morecomfort.

CASE 6 Mr. K. L.-Age 62 Years-Osteoarthritis

Knees, has had one cartlidge removed-unable to participate in sportswithout pain. Begam topical application of formulation used in Case 1.Increased ability to participate in sports. Improvement still maintainedin spite of acute flare-ups on occasion.

CASE 7 Mr. B. P.-Age 59 years-Acute Bursitis and Arthritis

Acute Bursities left shoulder. Abduction only 150. Acute pain in bothknees from degenerated cartilages and osteoarthritis. Patient begantopical treatment with penetrating solution comprising DMSO,anti-inflammatory, propylene glycol, glycerine and water afterarthroscopy and by the time his surgical booking had arrived, he was somuch improved he refused the surgical procedure. His pain graduallyreceded, mobility of knees and shoulder increased until he was able tolive in comfort and return to active work and sports without pain. Henow only requires occasional application of DMSO solution for slightdiscomfort.

CASE 8 Age 64 years

Patient diagnosed as having neuromuscular rheumatism and advisedprolonged bed rest-suggested period three years. Patient has markedcrepitus joints-had been told "her chances of working again werenon-existent" (Mayo Clinic). Patient was a practical nurse who hadre-entered a registered nursing training course but was forced to stopdue to illness-when first seen was in a wheel chair and even had greatdifficulty in swallowing. After treatment with penetrating solutioncomprising DMSO, anti-inflammatory, propylene, glycol glycerine andwater for several days, a slight increase in movement of joints wasdetectable. A month later, feels immensely better and flexion androtation of shoulders has increased dramatically. She has an excellentresponse. Subsequently returned to nursing school, works three nights aweek and has returned to driving an automobile. This patient hasobtained full function of joints and muscles; has completed her nursingtraining and has worked full time since. She has now entered the B.Sc.nursing training course and is doing very well.

As many changes can be made to the embodiments disclosed withoutdeparting from the scope of the invention, it is intended that allmaterial contained herein be interpreted as illustrative of theinvention and not in a limiting sense.

We claim:
 1. A deep and rapidly penetrating homogeneous solution fortopical application causing medicine to penetrate deeply into affectedparts of the body without irritating the skin or leaving a greasy filmon the skin when the solution is applied topically, the solutioncomprising:(a) between about 40% and about 85% DMSO by weight of thesolution; (b) a polyalcohol for assisting to retain moisture in the skinand prevent the skin from dehydrating; (c) dispersant for assisting todisperse the components in solution to provide a homogeneous solutionwhen applied and when penetrating the skin (d) a medicine (e) water. 2.The solution of claim 1, wherein the medicine is Naproxen, ethanol isadded as a solubilizing agent.
 3. The solution of claim 1, wherein themedicine is Nifedipine.
 4. The solution of claim 1, wherein the medicineis Diclofenac.
 5. The solution of claim 1, wherein the polyalcohol has3-5 carbon atoms.
 6. The solution of claim 2, wherein the polyalcoholhas 3-5 carbon atoms.
 7. The solution of claim 3, wherein thepolyalcohol has 3-5 carbon atoms.
 8. The solution of claim 4, whereinthe polyalcohol has 3-5 carbon atoms.
 9. The solution of claim 1,wherein the polyalcohol is glycerol (glycerine).
 10. The solution ofclaim 2, wherein the polyalcohol is glycerol (glycerine).
 11. Thesolution of claim 3, wherein the polyalcohol is glycerol (glycerine).12. The solution of claim 4, wherein the polyalcohol is glycerol(glycerine).
 13. The solution of claim 1, wherein the DMSO is presentbetween about 60% and about 70% by weight of the solution.
 14. Thesolution of claim 1, wherein the DMSO constitutes about 65% by weight ofthe solution.
 15. The solution of claim 1, wherein the dispersant ispropylene glycol.
 16. The solution of claim 2, wherein the DMSO ispresent between about 60% and about 70% by weight of the solution. 17.The solution of claim 2, wherein the DMSO constitutes about 65% byweight of the solution.
 18. The solution of claim 2, wherein thedispersant is propylene glycol.
 19. The solution of claim 3, wherein theDMSO is present between about 60% and about 70% by weight of thesolution.
 20. The solution of claim 3, wherein the DMSO constitutesabout 65% by weight of the solution.
 21. The solution of claim 3,wherein the dispersant is propylene glycol.
 22. The solution of claim 4,wherein the DMSO is present between about 60% and about 70% by weight ofthe solution.
 23. The solution of claim 4, wherein the DMSO constitutesabout 65% by weight of the solution.
 24. The solution of claim 4,wherein the dispersant is propylene glycol.
 25. The solution of claim 5,wherein the DMSO is present between about 60% and about 70% by weight ofthe solution.
 26. The solution of claim 5, wherein the DMSO constitutesabout 65% by weight of the solution.
 27. The solution of claim 5,wherein the dispersant is propylene glycol.
 28. The solution of claim 6,wherein the DMSO is present between about 60% and about 70% by weight ofthe solution.
 29. The solution of claim 6, wherein the DMSO constitutesabout 65% by weight of the solution.
 30. The solution of claim 6,wherein the dispersant is propylene glycol.
 31. The solution of claim 7,wherein the DMSO is present between about 60% and about 70% by weight ofthe solution.
 32. The solution of claim 7, wherein the DMSO constitutesabout 65% by weight of the solution.
 33. The solution of claim 7,wherein the dispersant is propylene glycol.
 34. The solution of claim 8,wherein the DMSO is present between about 60% and about 70% by weight ofthe solution.
 35. The solution of claim 8, wherein the DMSO constitutesabout 65% by weight of the solution.
 36. The solution of claim 8,wherein the dispersant is propylene glycol.
 37. The solution of claim 9,wherein the DMSO is present between about 60% and about 70% by weight ofthe solution.
 38. The solution of claim 9, wherein the DMSO constitutesabout 65% by weight of the solution.
 39. The solution of claim 9,wherein the dispersant is propylene glycol.
 40. The solution of claim10, wherein the DMSO is present between about 60% and about 70% byweight of the solution.
 41. The solution of claim 10, wherein the DMSOconstitutes about 65% by weight of the solution.
 42. The solution ofclaim 10, wherein the dispersant is propylene glycol.
 43. The solutionof claim 11, wherein the DMSO is present between about 60% and about 70%by weight of the solution.
 44. The solution of claim 11, wherein theDMSO constitutes about 65% by weight of the solution.
 45. The solutionof claim 11, wherein the dispersant is propylene glycol.
 46. Thesolution of claim 12, wherein the DMSO is present between about 60% andabout 70% by weight of the solution.
 47. The solution of claim 13,wherein the DMSO constitutes about 65% by weight of the solution. 48.The solution of claim 12, wherein the dispersant is propylene glycol.